Bone cements are used surgically to assist in the attachment of artificial implants to living bone and for bone repair and reconstruction. The most commonly used bone cements comprise polymers formed from a mixture of polymethylmethacrylate (PMMA) and a monomer, such as methylmethacrylate (MMA), reacting in the presence of a polymerization activator or reaction initiator. These conventional PMMA-based cements have several disadvantages. Typically, the excessive exotherm during the curing process of conventional cements may itself cause tissue damage. In addition, conventional cements are not easily degradable or absorbable in vivo. This may present both an increased risk of infection and/or an inflammatory reaction at the site and may inhibit the growth of new bone at the site.
Biodegradable polymers have become increasingly important for a variety of biomedical applications including biomedical implants, such as sutures, stents, and coatings applied to those implants, tissue engineering scaffolds, and soft-tissue adhesives. Segmented polyurethane elastomers in particular have come into wide use as biomaterials due to their superior mechanical properties and chemical versatility. PCT International Application Publication No. WO 2004009227 describes certain degradable polyurethane compositions for use as tissue engineering scaffolds. U.S. Pat. No. 6,306,177 by Felt, et al., describes certain degradable polyurethanes for in situ tissue repair. U.S. Patent Application Publication No. 20050013793 by Beckman, et al., also describes degradable polyurethanes for e.g., tissue engineering and particularly for bone repair and replacement. U.S. Pat. No. 4,829,099 by Fuller, et al., describes certain absorbable polyisocyanates for use as surgical adhesives. U.S. Pat. Nos. 8,002,843 and 7,985,414 by Knaack, et al., describe a biodegradable polyisocyante (such as lysine diisocyanate) with an optionally hydroxylated biomolecule to form a degradable polyurethane. U.S. Pat. No. 7,964,207 by Deslaurier, et al., describes porous, non-absorbable, osteoconductive polyurethane compositions having mechanical properties consistent for use in bone repair.
For the preparation of implantable polyurethanes, it is conventional to mix, in the operating room, pre-weighed amounts of a diisocyanate, a polyol, a chain extender and, optionally, a filler that is often ceramic-like, polymeric or a cellulosic material. Optionally, an antimicrobial agent, e.g., tobramycin, may be added to reduce the incidence of post-operative infection. The components are usually liquid at ambient temperature and require mixing liquids and, sometimes, liquids with solids in a suitable container using a suitable stirring mechanism.
Liquid component settable polymers (e.g., Kryptonite) in medical use traditionally require mixing and application of the activated polymer as a liquid. Polymers provided in this way are difficult to apply, may become slippery upon exposure to body fluids, stick to surgical gloves, instruments and fixation devices such as wires, plates and screws. In some instances, polymer misapplication may result in damage to medical devices, such as drains and catheters, during their removal.
Despite progress in the development of polyurethane-based biomedical materials, there remains a need for non-toxic, readily biodegradable or absorbable compositions having suitable mechanical properties for bone repair and reconstruction. The present invention provides polyurethane-based compositions suitable for use in bone repair and reconstruction, specifically as bone cements, bone substitutes or hemostatic agents.